Multimodal Therapy for Brain AVM

(TOBAS Trial)

Recruiting at 30 trial locations

Overseen By Daniel Roy, MD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Disqualifiers: Hemorrhagic presentation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Varies based on treatment modality

1000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the best way to manage brain arteriovenous malformations (AVMs), which are unusual connections between blood vessels in the brain. It compares different treatments, such as neurosurgery, radiation therapy, and embolization (blocking blood flow to the AVM), to determine which best prevents serious issues like strokes or death. The study also examines whether these treatments can make surgery or radiation safer and more effective. Individuals with a brain AVM who have not required emergency surgery due to bleeding might be suitable candidates for this trial. As an unphased trial, it offers patients the opportunity to contribute to advancing treatment options for brain AVMs.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the safety of treatments for brain arteriovenous malformations (AVMs) depends on the method used. Studies suggest that embolization can make AVM surgery safer by reducing bleeding during the operation, though it carries a risk of permanent nerve-related problems in about 8% of cases.

Neurosurgery for AVMs has demonstrated good results, with a high success rate in completely removing the AVM in most patients. However, there is a 4% chance of serious complications after surgery.

Radiation therapy (radiosurgery) also presents certain risks. While effective, some patients experience lasting nerve-related issues, occurring in about 5% of cases. Additionally, there is a 10% chance of developing radionecrosis, where brain tissue gets damaged after treatment.

Overall, each treatment has its risks, but many patients experience positive outcomes. It's important to consider these risks along with the potential benefits when evaluating participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the multimodal therapy for brain arteriovenous malformations (AVMs) because it combines several advanced techniques tailored to each patient's condition. Unlike the standard of care, which often involves standalone treatments like neurosurgery or radiation, this approach carefully integrates neurosurgery, radiation therapy, radiosurgery, and potentially curative embolization based on the AVM's size and operability. This comprehensive strategy aims to maximize effectiveness by customizing the treatment plan, offering the potential for better outcomes and reduced risks compared to traditional methods. By leveraging a multidisciplinary team's expertise, the treatment can be precisely targeted, offering hope for improved success rates in managing complex brain AVMs.

What evidence suggests that this trial's treatments could be effective for brain AVMs?

Research has identified several promising treatments for brain arteriovenous malformations (AVMs). In this trial, participants may receive different treatments as part of the interventional therapy arm. Surgery, one option, has proven very effective, with studies showing complete removal of 92% of AVMs. Radiation therapy, particularly stereotactic radiosurgery (SRS), has succeeded in 80–90% of cases for smaller AVMs. Embolization, which blocks blood flow to the AVM, can enhance results when used before surgery or SRS, reducing treatment failures from 20% to 10% in some studies. Together, these treatments offer several effective options for managing brain AVMs. ^{3 6 7 8 9}

Who Is on the Research Team?

Daniel Roy, MD

Principal Investigator

CHUM-Montreal

Are You a Good Fit for This Trial?

The TOBAS study is for patients with brain arteriovenous malformations (AVMs), which are tangles of abnormal blood vessels connecting arteries and veins in the brain. It's open to all such patients, except those needing urgent surgery due to bleeding effects from AVM.

Inclusion Criteria

I have a brain AVM.

Exclusion Criteria

I had surgery for a bleeding in my brain that needed immediate attention.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive interventional therapy (neurosurgery, radiosurgery, or endovascular procedures) or conservative management

Varies based on treatment modality

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on neurological events and status

10 years

Nested Trial on Embolization

Pre-surgical or pre-radiosurgery embolization of cerebral AVMs to decrease treatment failures

Varies based on treatment modality

What Are the Treatments Tested in This Trial?

Interventions

• Embolization
• Neurosurgery
• Radiation therapy

Trial Overview This trial explores whether medical management or interventional therapies like embolization, neurosurgery, or radiation—alone or combined—can significantly reduce death/stroke risks in AVM patients over a decade. It also examines if pre-treatment embolization can enhance the success of other treatments.

How Is the Trial Designed?

Group I: Interventional therapy Active Control 3 Interventions

Interventional therapies include: neurosurgery (surgical resection when the lesion is considered by a multidisciplinary team to be safely 'operable'); radiation therapy (when the AVM is smaller than 3 cm, and considered to not be safely 'operable'); radiosurgery, alone or in combination, with or without endovascular procedure; curative embolization (when the lesion is considered curable by embolization). Patients with AVMs that the multidisciplinary team judges could potentially benefit from endovascular treatment prior to surgical resection or radiation therapy will then also be pre-randomly allocated to embolization or to no embolization.

Group II: Conservative management (medical management) Active Control 1 Intervention

The conservative, or medical management arm, involves pharmacological therapy as deemed appropriate for medical symptoms as determined by the treating investigator. Should patients in the conservative management arm develop hemorrhage or infarction related to their AVM, they then potentially become candidates for interventional therapy.

Neurosurgery is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Neurosurgery for:

• Brain Arteriovenous Malformations (AVMs)
• Ruptured AVMs
• Unruptured AVMs

Approved in United States as Neurosurgery for:

• Brain Arteriovenous Malformations (AVMs)
• Ruptured AVMs
• Unruptured AVMs

Approved in Canada as Neurosurgery for:

• Brain Arteriovenous Malformations (AVMs)
• Ruptured AVMs
• Unruptured AVMs

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Centre Hospitalier Régional et Universitaire de Brest

Collaborator

Trials

9

Recruited

21,100+

Published Research Related to This Trial

Stereotactic radiosurgery using a linear accelerator with a multileaf collimator has shown promising safety and efficacy in treating brain arteriovenous malformations (AVMs), with 15 out of 16 small AVMs (less than 10 cc) completely obliterated after more than 3 years.

The treatment demonstrated a low complication rate, with only four transient complications and no permanent ones, suggesting that this method is safe for patients, especially for larger AVMs that may require staged therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery of cerebral arteriovenous malformations with a multileaf collimator and a single isocenter. Ross, DA., Sandler, HM., Balter, JM., et al.[2019]

In a study of 115 patients with cerebral arteriovenous malformations (AVMs), a multidisciplinary approach combining surgery, embolization, and gamma radiosurgery resulted in a treatment success rate of 76.4%, with 41.7% achieving complete cure.

The treatment methods had a low complication rate, with only 4.8% experiencing permanent morbidity and 1.2% mortality, indicating that this combined approach is both effective and relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Multidisciplinary treatment of cerebral arteriovenous malformations: preliminary results in 115 consecutive patients]. van Rooij, WJ., Sluzewski, M., Wijnalda, D., et al.[2016]

In a study of 25 patients with larger arteriovenous malformations (AVMs) treated with stereotactic radiosurgery (SRS), significant predictors of adverse radiation effects (ARE) included lower vein-artery ratios, longer transit times, and higher radiation doses, highlighting the importance of vascular characteristics in treatment outcomes.

Asymptomatic parenchymal effects occurred in 52% of patients, with 16% experiencing symptomatic effects, indicating that while SRS can be effective, careful monitoring of vascular parameters is essential to minimize risks of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative Analysis of Parenchymal Effects and Flow of Large Arteriovenous Malformations Managed With Stereotactic Radiosurgery. Alzate, JD., Mashiach, E., Bernstein, K., et al.[2023]

Endovascular embolization is a key component in the modern management of cerebral arteriovenous malformations (AVMs), as it reduces the volume of the AVM nidus and addresses associated risks like aneurysms and fistulas.

This technique not only prepares AVMs for surgical resection but also enhances the effectiveness of subsequent treatments like stereotactic radiosurgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endovascular treatment of cerebral arteriovenous malformations. Gailloud, P.[2013]

Gamma Knife radiosurgery (GKRS) is a safe and effective noninvasive treatment for brain arteriovenous malformations (AVMs), with a complete obliteration rate of 46.1% across different nidus types in a study of 154 patients over an average follow-up of 52 months.

The study found no significant differences in complication rates or obliteration outcomes between compact and diffuse-type AVMs, suggesting that GKRS can be applied effectively regardless of nidus characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Gamma Knife Radiosurgery for Brain Arteriovenous Malformations According to Nidus Type. Koo, JH., Hwang, EH., Song, JH., et al.[2023]

In a study of 24 patients with large brain arteriovenous malformations (AVMs), the combination of particulate embolization and stereotactic radiosurgery resulted in a 50% complete obliteration rate, which is comparable to the 58% rate seen in smaller AVMs treated with radiosurgery alone.

While some recanalization of embolized AVM segments occurred in 12% of patients, the overall long-term occlusion rates were high, and the combined treatment approach was found to be more effective than using radiosurgery alone for large AVMs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of particulate embolization combined with stereotactic radiosurgery for treatment of large arteriovenous malformations of the brain. Mathis, JA., Barr, JD., Horton, JA., et al.[2021]

Stereotactic radiosurgery has been successfully used for over 40 years to treat cerebral arteriovenous malformations, achieving complete obliteration rates of 30-50% after 1 year and 72-90% after 2 years, highlighting its efficacy based on patient selection.

Radiosurgery is also effective for treating acoustic neurinomas and pituitary tumors, with over 90% tumor growth control and approximately 50% hearing preservation, making it a noninvasive alternative to traditional surgery with lower morbidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiation therapy and radiosurgery. Ostertag, CB.[2018]

The study involved 294 patients treated for 304 intracranial arteriovenous malformations (AVMs) over a 10-year period, showcasing a comprehensive approach to managing these complex conditions.

The multimodality management concept, which includes microsurgery, embolization, and gamma knife radiosurgery, suggests a potentially effective strategy for treating AVMs, although specific outcomes and efficacy details are not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodality Management of Cerebral Arteriovenous Malformations with Special Reference to AVM-Related Hemorrhages During Ongoing Staged Treatment. Gruber, A., Bavinzski, G., Kitz, K., et al.[2017]

In a study of 119 patients with brain arteriovenous malformations (AVMs), combined endovascular embolization and surgical treatment resulted in disabling complications in 5% of cases and nondisabling new deficits in 42%, indicating a significant risk of neurologic impairment after treatment.

Factors such as nonhemorrhagic AVM presentation, deep venous drainage, location in eloquent brain regions, and larger AVM size were associated with a higher likelihood of treatment-related neurologic deficits, suggesting that these characteristics should be considered when planning AVM therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determinants of staged endovascular and surgical treatment outcome of brain arteriovenous malformations. Hartmann, A., Mast, H., Mohr, JP., et al.[2022]

Proton beam treatment effectively reduces the size of cerebral arteriovenous malformations (AVMs), with significant volume reductions observed in patients with AVMs larger than 10 ml, indicating its efficacy as a treatment option.

The treatment has an acceptable safety profile, with most patients experiencing minimal adverse effects, and a high rate of seizure freedom in patients with epilepsy, suggesting it is a valuable alternative to other irradiation methods for larger AVMs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated, stereotactic proton beam treatment of cerebral arteriovenous malformations. Silander, H., Pellettieri, L., Enblad, P., et al.[2019]

The study evaluated a new hybrid surgical suite for treating cerebral arteriovenous malformations (AVMs) in 25 patients, demonstrating that intraoperative imaging can effectively identify small AVM remnants, allowing for complete resections during the same procedure.

The integrated approach improved workflow and safety, as all necessary diagnostic and therapeutic steps were performed without moving patients, reducing the need for additional surgeries and enhancing the overall treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative angiography reloaded: a new hybrid operating theater for combined endovascular and surgical treatment of cerebral arteriovenous malformations: a pilot study on 25 patients. Kotowski, M., Sarrafzadeh, A., Schatlo, B., et al.[2013]

A study of 33,997 patients with cerebral arteriovenous malformations (AVMs) from 2001 to 2009 revealed that while treatment costs doubled, there were no significant improvements in patient outcomes, indicating a need for better assessment of treatment value.

The use of endovascular treatments for AVMs increased significantly during the study period, while microsurgical treatment rates remained stable, highlighting the need for further research to determine which treatment modalities are most effective for different patient demographics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of treatments for cerebral arteriovenous malformations: trends in nationwide outcomes from 2000 to 2009. Davies, JM., Yanamadala, V., Lawton, MT.[2022]

Radiosurgery effectively treats small intracranial tumors and arteriovenous malformations (AVMs) using precise radiation delivery, with applications for both malignant tumors (like brain metastases and gliomas) and benign tumors (such as meningiomas and acoustic neuromas).

Most patients experience clinical improvement with radiosurgery, and it generally results in less morbidity compared to traditional surgical resection, despite the potential for complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical uses of radiosurgery. Chang, SD., Adler, JR., Hancock, SL.[2006]

Proton beam therapy was used to treat 709 patients with inaccessible arteriovenous malformations (AVMs), showing a low risk of injury to normal brain tissue and a follow-up period of over 2 years for 92% of patients.

While proton beam therapy is generally safe, the effectiveness of the treatment can decrease if the therapeutic doses are not sufficient, highlighting the importance of delivering adequate doses for successful outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Bragg peak proton beam radiosurgery for cerebral arteriovenous malformations. Kjellberg, RN.[2004]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38842298/

A Systematic Review of Literature and Meta-Analysis Curative embolization of AVM is primarily reserved for small and low-grade AVMs, with highly variable outcomes.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37226884/

Association of embolization with long-term outcomes in ... This prospective cohort study did not support a substantial superiority of embolization over conservative management for AVMs in preventing long-term ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1878875023011762

Preradiosurgical Embolization of Arteriovenous ... Total obliteration after SRS was achieved in 56 AVMs (67.5%) after 2 years, and in 38 (86.4%) after 4 years. Two (2.4%) patients had rehemorrhage after SRS.

4. jnis.bmj.com jnis.bmj.com/content/16/6/541

Preoperative embolization of brain arteriovenous ... This study provides an objective quantification of the impact of preoperative embolization on the treatment strategy for brain AVMs, supporting its efficacy in ...

5. frontiersin.org frontiersin.org/journals/surgery/articles/10.3389/fsurg.2025.1563256/full

Impact of embolization on stereotactic radiosurgery ... This systematic review and meta-analysis aim to evaluate the effects of embolization on SRS outcomes in high-grade AVMs.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9086959/

Impact of Pre-operative Embolization With Onyx for Brain ... Pre-operative embolization with Onyx can significantly reduce the amount of intraoperative bleeding in AVM resection and may contribute to safe AVM surgery.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9160113/

Preoperative embolisation of brain arteriovenous ... Of the 1661 citations, 8 studies with 588 patients met predefined inclusion criteria. No studies specifically compared outcomes of surgical ...

8. thejns.org thejns.org/view/journals/j-neurosurg/138/5/article-p1393.xml

Endovascular treatment of brain arteriovenous malformations The Treatment of Brain AVMs Study (TOBAS) is an all-inclusive pragmatic study that comprises two randomized trials and multiple registries.

9. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.124.049109?doi=10.1161/STROKEAHA.124.049109

Transvenous Approach for the Treatment of Cerebral ... Evaluating the safety and efficacy of transvenous embolization for brain arteriovenous malformation: a systematic review and meta-analysis.